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Long-term administration of aspirin inhibits tumour formation and triggers anti-neoplastic molecular changes in a pre-clinical model of colon carcinogenesis.

Authors: Bousserouel, S  Gosse, F  Bouhadjar, M  Soler, L  Marescaux, J  Raul, F 
Citation: Bousserouel S, etal., Oncol Rep. 2010 Feb;23(2):511-7.
Pubmed: (View Article at PubMed) PMID:20043115

Despite numerous studies aimed at verifying the anti-tumour activity of aspirin on colon carcinogenesis little is known on the molecular targets involved in the anti-carcinogenic properties of this drug. We investigated the long-term administration of low dose of aspirin in a model of experimental colon carcinogenesis in rats. Adult Wistar rats received an intraperitoneal injection of azoxymethane (AOM) once a week for two weeks in order to initiate colon carcinogenesis. One week after AOM injection, rats received daily 0.01% aspirin (6 mg/kg body weight) in drinking water for 10 months. Compared to AOM control rats, aspirin treatment for 10 months caused a 50% reduction of the number of aberrant crypt foci associated with a 50% reduction of prostaglandin E2 (PGE2) concentration and suppressed by 80% tumour formation in the colon. RT-PCR quantitative analysis showed that aspirin treatment reduced significantly (P<0.01) the AOM-triggered increase in mRNA levels of soluble inflammatory mediators (TNFalpha and IL-1beta) and metalloproteinases (MMP3 and MMP7). Conversely, we detected an increased expression level of alpha-defensin-5 (Rd-5, 2 fold) and lipocalin-2 (LCN2, 4 fold), two markers of the innate immunity system. The expression of apoptosis-related genes such as death receptors and their ligands were reduced by aspirin and the Bcl-2/Bax transcript ratio droped, Bcl-2 expression being reduced to the level found in saline control rats. The present study identifies new molecular targets triggered by aspirin in the colonic mucosa and may support the use of non-toxic low dose of aspirin in long-term treatments as a prophylactic approach against colon carcinogenesis.

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CRRD Object Information
CRRD ID: 2316492
Created: 2010-02-12
Species: All species
Last Modified: 2010-02-12
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.